Nutritional Support For Acute Kidney Injury (Review) : Li Y, Tang X, Zhang J, Wu T

Nutritional support for acute kidney injury (Review)
Li Y, Tang X, Zhang J, Wu T
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2012, Issue 9 http://www.thecochranelibrary.com
Nutritional support for acute kidney injury (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
TABLE OF CONTENTS HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.1. Comparison 1 Essential L-amino acids (ELAA) versus glucose, Outcome 1 Recovery from acute kidney injury. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.2. Comparison 1 Essential L-amino acids (ELAA) versus glucose, Outcome 2 Survival on dialysis. . . . Analysis 1.3. Comparison 1 Essential L-amino acids (ELAA) versus glucose, Outcome 3 Average slope of serum creatinine. Analysis 1.4. Comparison 1 Essential L-amino acids (ELAA) versus glucose, Outcome 4 Average slope of blood urea nitrogen. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.5. Comparison 1 Essential L-amino acids (ELAA) versus glucose, Outcome 5 Serum creatinine. . . . . Analysis 1.6. Comparison 1 Essential L-amino acids (ELAA) versus glucose, Outcome 6 Serum proteins. . . . . Analysis 1.7. Comparison 1 Essential L-amino acids (ELAA) versus glucose, Outcome 7 Urea nitrogen appearance. . Analysis 2.1. Comparison 2 High essential and nonessential amino acid (ENAA) nitrogen intake versus low essential amino acid (EAA) nitrogen intake, Outcome 1 Urea nitrogen appearance. . . . . . . . . . . . . . . . Analysis 2.2. Comparison 2 High essential and nonessential amino acid (ENAA) nitrogen intake versus low essential amino acid (EAA) nitrogen intake, Outcome 2 Estimated protein nitrogen balance. . . . . . . . . . . . . Analysis 3.1. Comparison 3 Essential amino acids (EAA) versus general amino acids (GAA), Outcome 1 Death. . . Analysis 3.2. Comparison 3 Essential amino acids (EAA) versus general amino acids (GAA), Outcome 2 Estimated protein nitrogen balance. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 3.3. Comparison 3 Essential amino acids (EAA) versus general amino acids (GAA), Outcome 3 Urea nitrogen appearance. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 3.4. Comparison 3 Essential amino acids (EAA) versus general amino acids (GAA), Outcome 4 Net protein utilisation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 4.1. Comparison 4 High-dose amino acids (AA) versus normal-dose AA, Outcome 1 Death. . . . . . . Analysis 4.2. Comparison 4 High-dose amino acids (AA) versus normal-dose AA, Outcome 2 Haemodialysis requirement. Analysis 4.3. Comparison 4 High-dose amino acids (AA) versus normal-dose AA, Outcome 3 Cumulative nitrogen balance. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 4.4. Comparison 4 High-dose amino acids (AA) versus normal-dose AA, Outcome 4 Furosemide requirement. Analysis 5.1. Comparison 5 Glucose+EAA+histidin versus glucose+GAA, Outcome 1 Nitrogen balance. . . . . . Analysis 5.2. Comparison 5 Glucose+EAA+histidin versus glucose+GAA, Outcome 2 Plasma urea. . . . . . . . Analysis 5.3. Comparison 5 Glucose+EAA+histidin versus glucose+GAA, Outcome 3 U/P urea. . . . . . . . . Analysis 5.4. Comparison 5 Glucose+EAA+histidin versus glucose+GAA, Outcome 4 Serum creatinine. . . . . . Analysis 5.5. Comparison 5 Glucose+EAA+histidin versus glucose+GAA, Outcome 5 Urea nitrogen appearance. . . Analysis 5.6. Comparison 5 Glucose+EAA+histidin versus glucose+GAA, Outcome 6 Serum proteins. . . . . . Analysis 6.1. Comparison 6 Glucose+EAA+histidin versus glucose+nitrogen+fat, Outcome 1 Nitrogen balance. . . Analysis 6.2. Comparison 6 Glucose+EAA+histidin versus glucose+nitrogen+fat, Outcome 2 Plasma urea. . . . . Analysis 6.3. Comparison 6 Glucose+EAA+histidin versus glucose+nitrogen+fat, Outcome 3 U/P urea. . . . . . Analysis 6.4. Comparison 6 Glucose+EAA+histidin versus glucose+nitrogen+fat, Outcome 4 Serum creatinine. . .
1 1 2 2 3 3 5 6 7 8 12 13 13 14 16 26 28 28 29 29 30 30 31 31 32 32 33 33 34 34 35 35 36 36 37 37 38 38 39 39 40 40 41
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Analysis 7.1. Comparison 7 Glucose+GAA versus glucose+nitrogen+fat, Outcome 1 Nitrogen balance. Analysis 7.2. Comparison 7 Glucose+GAA versus glucose+nitrogen+fat, Outcome 2 Plasma urea. . . Analysis 7.3. Comparison 7 Glucose+GAA versus glucose+nitrogen+fat, Outcome 3 U/P urea. . . . Analysis 7.4. Comparison 7 Glucose+GAA versus glucose+nitrogen+fat, Outcome 4 Serum creatinine. APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . WHATS NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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[Intervention Review]
Nutritional support for acute kidney injury

Yi Li1 , Xi Tang2 , Juqian Zhang2 , Taixiang Wu3 of Intensive Care Unit, Sichuan Cancer Hospital, Chengdu, China. 2 Department of Nephrology, West China Hospital, Sichuan University, Chengdu, China. 3 Chinese Cochrane Centre, Chinese Clinical Trial Registry, Chinese Evidence-Based Medicine Centre, INCLEN Resource and Training Centre, West China Hospital, Sichuan University, Chengdu, China Contact address: Taixiang Wu, Chinese Cochrane Centre, Chinese Clinical Trial Registry, Chinese Evidence-Based Medicine Centre, INCLEN Resource and Training Centre, West China Hospital, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, Sichuan, 610041, China. txwutx@hotmail.com. Editorial group: Cochrane Renal Group. Publication status and date: Stable (no update expected for reasons given in Whats new), published in Issue 9, 2012. Review content assessed as up-to-date: 4 July 2012. Citation: Li Y, Tang X, Zhang J, Wu T. Nutritional support for acute kidney injury. Cochrane Database of Systematic Reviews 2012, Issue 8. Art. No.: CD005426. DOI: 10.1002/14651858.CD005426.pub3. Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
1 Department
ABSTRACT Background Treatment for acute kidney Injury (AKI) primarily relies on treating the underlying cause and maintaining the patient until kidney function has recovered. Enteral and parenteral nutrition are commonly used to treat nutritional disorders in AKI patients, however their efcacy in treating AKI are still debated. This review was rst published in 2010. Objectives To evaluate the effectiveness and safety of nutritional support for patients with AKI. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Chinese Biomedical Disc, VIP and China National Knowledge Infrastructure (CNKI). Date of last search: 4 July 2012 Selection criteria All randomised controlled trials (RCTs) reported for AKI and nutrition were included. Data collection and analysis Authors independently assessed study quality and extracted data. Results were expressed as risk ratio (RR) with 95% condence intervals (CI) or mean difference (MD). Main results Eight studies (257 participants) were included. An overall pooled analysis was not performed due to the different interventions used and different outcomes measured. Selection bias was not reported (unclear) in six studies and was adequately reported (low) for random sequence generation in two studies. Participant/personnel blinding was adequately reported in one study and unclear in seven. Incomplete outcome reporting bias was low in six studies and high in two. Selective reporting was low in six studies, unclear in one study, and high in one study. No other biases were detected. There was a signicant increase in recovery rate for AKI (RR 1.70,
Nutritional support for acute kidney injury (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 1
95% CI 1.70 to 2.79) and survival in dialysed patients (RR 3.56, 95% CI 0.97 to 13.08) for intravenous essential L-amino acids (EAA) compared to hypertonic glucose alone. Compared to lower calorie-total parenteral nutrition (TPN), higher calorie-TPN did not improve estimated nitrogen balance, protein catabolic rate, or urea generation rate; but increased serum triglycerides, glucose, insulin need and nutritional uid administration. There was no difference between groups in estimated nitrogen balance, but there were differences between urea nitrogen appearance (MD 0.98, 95% CI 0.25 to 1.71) and net protein utilisation (MD 21.50%, 95% CI 0.39 to 42.61). Urea nitrogen appearance was lower in the low nitrogen intake group than in the high nitrogen intake group. There was no signicant difference in death between EAA and general amino acids (GAA) (RR 1.52, 95% CI 0.63 to 3.68). High dose amino acids did not improve cumulative water excretion, furosemide requirement, nitrogen balance or death compared to normal dose amino acids. Glucose+EAA+histidin had better nitrogen balance than glucose+GAA; glucose+nitrogen+fat signicantly increased serum creatinine compared with glucose+GAA; glucose+EAA+histidin signicantly improved nitrogen balance, U/P urea and serum creatinine, but increased plasma urea compared to glucose+nitrogen+fat. Authors conclusions There was insufcient evidence found to support the effectiveness of nutritional support for AKI. Further high quality studies are required to provide reliable evidence of the effect and safety of nutritional support.
PLAIN LANGUAGE SUMMARY Nutritional support for acute kidney injury Maintaining nutritional balance is vital in treating patients with acute kidney injury (AKI). Nutritional therapies, including parenteral nutrition (delivered via injection) and enteric (oral) nutrition are widely used. Eight randomised controlled trials (257 participants) were included in this review. Essential L-amino acids may shorten the overall duration of kidney dysfunction and improved survival from AKI. However, due to the small number of participants and the poor quality of some studies, we are unable to provide recommendations for the use of nutritional support for treating AKI.
BACKGROUND
1999). In some patients with shock or sepsis and non functioning gastrointestinal tract, the death rate can reach 80% to 90%. Approximately 30% of admissions to intensive care units (ICU) develop AKI (Hou 1983), and half of these patients will die. Infection accounts for three quarters of these deaths with cardiorespiratory complications and cardiovascular disease the next most common causes of death (Feest 1993; Santacruz 1996). The mortality in elderly patients with all forms of AKI is 53%, while paediatric patients with AKI have a mortality averaging 25%. Over the past 30 years, the survival rate for AKI has not improved, primarily because affected patients are now older and have more comorbid conditions (Feest 1993; Finn 1993; Thadhani 1996).
Description of the condition

Acute kidney injury (AKI) is characterised by a rapid (hours to weeks) decline in glomerular ltration rate (GFR) and retention of nitrogen waste products such as blood urea nitrogen (BUN) and creatinine (Anderson 1980). AKI is a syndrome caused by many different diseases and mechanisms. Clinical characters include albuminuria, hypertension, oedema, is usually associated with oliguria (urine output < 30 mL/h or < 400 mL/d), although urine output may be normal or increased (Thadhani 1996). According to the denition proposed by Acute Kidney Injury Network based of the RIFLE classication, AKI is the third stage of AKI, which characterised by the increase in serum creatinine (SCr) to more than 300% from baseline (or SCr 4.0 mg/dL with an acute increase of at least 0.5 mg/dL (44 mol/L), or the urine output less than 0.3 mL/kg/h for 24 hours or anuria for 12 hours. AKI is a complication in critically ill patients and has a persistently high mortality rate in hospitalised patients (40% to 60%) (Fiaccadori
Description of the intervention

Treatment for AKI primarily relies on treating the underlying cause and maintaining the patient until kidney function has recovered. This will include, correcting uid, electrolyte and uraemic abnormalities, treating infections and maintaining nutrition. Renal re2
placement therapy (RRT) may be required for uncontrolled hyperkalaemia, acidosis or severe uid overload (Schif 1994). Intrarenal AKI (caused by direct injury to the kidneys including ischaemic hypoxic insults, renal artery obstruction, or renal vein occlusion) can be treated using glucocorticoids (such as cortisol), cyclophosphamide or other medication. In most cases of postrenal AKI (caused by blockage in the urinary tract) kidney function rapidly returns to normal upon removal of the obstruction. Recent studies report that in cells which recover from an ischaemic insult, growth factors may play a role in recovery, such as epidermal growth factor, insulin-like growth factor or hepatocyte-type growth factor for intrarenal AKI (Fouque 1998).
1983). In patients this has not been well documented. The effectiveness and safety of such treatment needs to be reviewed systematically and appraised critically to inform current practice.
OBJECTIVES
To assess the effects and acceptability of nutritional support in adults and children for treating AKI in hospitalised patients.
METHODS How the intervention might work

In hypercatabolic AKI, where patients become nutritionally decient in protein, energy requirements will exceed those that are conventionally prescribed (Spreiter 1980). Thus nutritional care is particularly important because patients suffer not only from uraemia, metabolic acidosis, and uid and electrolyte imbalance, but also from physiological stress (e.g. infection, tissue destruction or poisoning) which increases protein needs. Total caloric intake should be 30 to 45 kcal (126 to 189 kJ)/kg/d, and should come from a combination of carbohydrates and lipids. In patients not receiving dialysis, protein intake should be restricted to 0.6 g/kg/ d, whereas patients on dialysis should have a protein intake of 1 to 1.5 g/kg/d (Wolfson 1993). Some studies recommend a multifaceted approach using total parenteral nutrition (TPN) with essential and nonessential amino acids (ENAA) and possibly a larger proportion of the branched-chain amino acids, higher energy intake, anabolic agents, and continuous arterio-venous haemoltration. These measures should improve morbidity and mortality (Feinstein 1983). The need for glutamine supplementation in dialysis patients with AKI is greater in the rst days of continuous veno-venous haemodialtration (Novak 1997) and vitamin supplementation is often inadequate and should be re-evaluated (Druml 1998). Continuous RRT results in signicant losses of selenium, copper, and thiamine (Berger 2004). Some recent studies suggest that parenteral nutrition leads to more infection compared to no nutritional therapy (Koretz 2001). A systematic review has suggested that enteric nutrition failed to show any clinical benet compared to no nutritional therapy in critical ill patients (Koretz 2007). Whether artical nutrition is important in a variety of diseases, including AKI remains controversial.
Criteria for considering studies for this review
Types of studies All randomised controlled trials (RCTs) investigating the use of nutritional support in adults and children with AKI. The rst period of randomised cross-over studies were also included. Types of participants All patients suffering from moderate to severe AKI, as estimated by either SCr, creatinine clearance (CrCl) or GFR measurement, regardless of sex or age. Ideally, the diagnostic criteria for AKI should have been described in the study. To be consistent with changes in classication and diagnostic criteria of the disease, the diagnosis should have been established using the standard criteria valid at the time of the study. Changes in diagnostic criteria may produce signicant variability in the clinical characteristics of the patients included as well as in the results obtained. These differences were to be considered, documented, and explored in a sensitivity analysis. Types of interventions One nutritional support pattern compared with nothing, placebo (e.g. a low energy drink) or different support patterns, or other current regime (e.g. using no supplement or an alternative supplement with a different amount of calories and protein) were considered. Interventions aimed at improving the intake of protein and energy using enteric or parenteral nutrition (EN or PN). Protein could be provided together with non-protein energy sources such as carbohydrate and fat, and with or without added minerals and vitamins. Although protein-only supplementation has occasionally been used for experimental purposes, it has not be considered for routine use and was therefore excluded.
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Why it is important to do this review

It is important to identify those who would benet from nutritional support and to dene the optimal time to initiate the support (Druml 1998). In experimental animals, provision of amino acids or TPN accelerated tissue repair and recovery of AKI (Toback
We were interested in supplements in the form of: TPN Total enteral nutrition EN and PN Immunomodulatory supplements or supplements of specic amino acids. We planned to explore the following potential sources of heterogeneity using subgroup analyses or meta-regression: Intervention (essential amino acids (EAA), general amino acids (GAA), ENAA, calories, nitrogen) TPN, EN, placebo or no nutritional therapy Dose (nitrogen, amino acids, calories) Patients in and out of ICU
Additional outcome measures
1. Participants perceived quality of life, ideally using a validated scale 2. Length of hospital stay (hospitalised patients only) 3. Level of care and support required 4. Number of hospital admissions/readmissions 5. Compliance with intervention (proportion of the supplement provided which was consumed, alone or with assistance) 6. Economic outcomes
Search methods for identication of studies

Relevant studies were obtained from the following sources (see Appendix 1 for electronic search strategies).
Types of outcome measures
Kidney function measures
Electronic searches We searched the Cochrane Renal Groups Specialised Register (4 July 2012) through contact with the Trials Search Co-ordinator using search terms relevant to this review. The Cochrane Renal Groups Specialised Register contains studies identied from: 1. Quarterly searches of the Cochrane Central Register of Controlled Trials CENTRAL; 2. Weekly searches of MEDLINE OVID SP; 3. Handsearching of renal-related journals & the proceedings of major renal conferences; 4. Searching of the current year of EMBASE OVID SP; 5. Weekly current awareness alerts for selected renal-journals; 6. Searches of the International Clinical Trials Register (ICTRP) Search Portal & ClinicalTrials.gov Studies contained in the specialised register are identied through search strategies for CENTRAL, MEDLINE, and EMBASE based on the scope of the Cochrane Renal Group. Details of these strategies as well as a list of handsearched journals, conference proceedings and current awareness alerts are available in the Specialised Register section of information about the Cochrane Renal Group. See Appendix 1 for search terms used in strategies for this review. We also search the following electronic databases. 1. Chinese Biomedical Disc (CBMDisc from 1978). 2. VIP Chinese Science and Technique Journals Database (from 1989). 3. China National Knowledge Infrastructure (CNKI) (from 1994).
1. All-cause mortality 2. Morbidity, number of people with complications (e.g. pressure sores, deep vein thrombosis, respiratory and urinary infections). 3. Survival, survival from AKI 4. Recovery, number of people recovered from AKI 5. Haemodialysis (number of people needing haemodialysis) 6. Maintenance dialysis (number of people need haemodialysis for low or no kidney function) 7. BUN 8. SCr 9. Average slope of SCr/BUN level
Nutritional status measures
1. Subjective Global Assessment: history (weight changes, dietary intake, gastrointestinal symptoms) and physical examination (loss of subcutaneous fat, muscle wasting, oedema) 2. Anthropometric parameters 3. Biochemical parameters 4. Immunologic parameters 5. Nitrogen balance 6. Urea nitrogen appearance and estimated protein balance 7. Net protein utilisation 8. Urea generation rate
Adverse effect outcome measures
1. 2. 3. 4. 5.
Glucose level Triglycerides level Insulin use Volume Catheter infection
Searching other resources 1. Reference lists of nephrology textbooks, review articles and relevant studies.
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2. Letters seeking information about unpublished or incomplete studies to investigators known to be involved in previous studies.
Data synthesis For dichotomous outcomes (e.g. death, haemodialysis) results were expressed as risk ratios (RR) with 95% condence intervals (CI) and continuous scales of measurement (e.g. SCr, CrCl) were expressed by mean difference (MD) with 95% CI. We were unable to perform combined analysis due to clinical heterogeneity between studies.
Data collection and analysis
Selection of studies One author searched and retrieved studies. Two authors determined which studies satised the inclusion criteria.
RESULTS
Data extraction and management Data extraction was carried out by the same authors. There was no disagreement between authors in the searching and inclusion of studies. Assessment of risk of bias in included studies The following items will be independently assessed by two authors using the risk of bias assessment tool (Higgins 2011) (see Appendix 2). Was there adequate sequence generation (selection bias)? Was allocation adequately concealed (selection bias)? Was knowledge of the allocated interventions adequately prevented during the study (detection bias)? Participants and personnel Outcome assessors Were incomplete outcome data adequately addressed (attrition bias)? Are reports of the study free of suggestion of selective outcome reporting (reporting bias)? Was the study apparently free of other problems that could put it at a risk of bias? Results of the search The initial search yielded 687 papers. Of these, 19 studies appeared to potentially full our inclusion criteria. Eight studies did not randomly allocate the participants. Two studies (Berg 2007; Berger 2008) enrolled patients with other disease besides acute renal failure. One study (Smolle 1997) aimed to test the plasma concentration of amino acids but the study was not related to kidney function. One studys data was unusable (Blumenkrantz 1978), leaving eight studies suitable for inclusion in this systematic review (Abel 1973; De Aguilar 1982; Feinstein 1981; Feinstein 1983; Fiaccadori 2005; Martinez 1980; Mirtallo 1982; Singer 2007). Two studies were published in Spanish, and the others were published in English. Study ow diagram of included studies is showed in Figure 1.
Description of studies
See: Characteristics of included studies; Characteristics of excluded studies.
Figure 1. Study ow diagram of included studies
This update identied an additional 32 papers published between 2009 and 2012. After assessment; none met our inclusion criteria. Included studies
Participants
respectively in two phases, while all the patients included in Singer 2007 had non-oliguric AKI with a CrCl < 50 mL/min and conserved diuresis > 2000 mL/d. In Singer 2007, patients in group two were signicantly older (P < 0.05). None of the other studies had signicant differences between the treatment and control group at baseline.
Interventions
A total of 257 participants were included. Mirtallo 1982 included 41 patients with AKI and 4 patients who had chronic kidney disease with superimposed acute illness. De Aguilar 1982 and Martinez 1980 included 94 patients with AKI in the polyuria phase during a bacteraemia episode. Martinez 1980 included one patient with gram-positive and 34 patients with gram-negative bacteriaemia. De Aguilar 1982 included 59 patients with gram-negative bacteriaemia. Fiaccadori 2005 and Singer 2007 were performed in ICU patients, so the patients included were more severe and with critical underlying diseases. Thirty patients from two centres were included in Feinstein 1981, with hypotension or sepsis as the main cause of AKI. Fiaccadori 2005 included 10 patients (mean age 72 years) using the treatment intervention and compared intervention
All studies gave IV nutritional supplements to patients. Abel 1973 compared eight essential L-amino acids (ELAA) (13.1g/d) and vitamins with hypertonic glucose with vitamins for 15 days. De Aguilar 1982 and Martinez 1980 compared three interventions: glucose (2000 Kcal) and EAA (4.38 g/d) with histidin, glucose and GAA, glucose and GAA and intralipid. Fiaccadori 2005 compared a higher calorie-TPN regimen (40 kcal/kg/d) with a lower calorie-TPN regimen (30 kcal/kg/d) each for three days with a nitrogen intake of 0.25 g/kg/d for both regimens. Feinstein 1981 compared glucose alone, 21.2 g EAA and 42.1 g GAA.
Feinstein 1983 compared high nitrogen intakes (11.3 g/d on average) containing ENAA with low nitrogen intakes (2.3 g/d in average) contained only EAA. Mirtallo 1982 compared EAA (17 g/L) with GAA (20 g/L) infusion. Singer 2007 compared high-dose amino acids (150 g/d) with normal-dose amino acids (75 g/d) infusion.
Outcome measures
Two studies assessed mortality (Mirtallo 1982; Singer 2007). Although Singer 2007 did not analyse mortality directly, we were able to extract the data for statistical analysis. Six studies (De Aguilar 1982; Feinstein 1981; Feinstein 1983; Fiaccadori 2005; Martinez 1980; Mirtallo 1982) reported at least measurement of urea nitrogen appearance and estimated nitrogen balance to evalu-
ate nutritional status. Mirtallo 1982 also assessed net protein utilisation. Singer 2007 not only recorded nitrogen balance as a nutritional measurement, but also recorded furosemide and dialysis rate. Abel 1973 assessed recovery from AKI, survival on dialysis, average slope of SCr level and average slope of BUN measurements of recovery of kidney function. Fiaccadori 2005 assessed nitrogen balance by calculating the difference between nitrogen intake and nitrogen lost, protein catabolic rate, urea generation rate, triglycerides, glucose, insulin use and nutritional uid administration. Four studies (Abel 1973; Feinstein 1983; Fiaccadori 2005; Mirtallo 1982) mentioned complications, but there were no data available for analysis.
Risk of bias in included studies

Risk of bias in included studies is showed in Figure 2 and Figure 3.
Figure 2. Risk of bias graph: review authors judgements about each risk of bias item presented as percentages across all included studies.
Figure 3. Risk of bias summary: review authors judgements about each risk of bias item for each included study.
Study design Of the eight studies, seven were parallel RCTs (Abel 1973; De Aguilar 1982; Feinstein 1981; Feinstein 1983; Martinez 1980; Mirtallo 1982; Singer 2007) and one was a randomised crossover study (Fiaccadori 2005).
Other potential sources of bias All studies appeared to free of any other potential biases.
Effects of interventions
Four studies were performed in ICUs, and four were performed in a general ward. We did not combined studies because interventions and doses were different for each study. Separate outcomes for the included studies are presented as RR and MD with their 95% CI. Four studies described the complications but didnt provide data suitable for statistical analysis. Planned subgroup and sensitivity analyses were not performed as we were not able to combine the studies. Essential L-amino acids (ELAA) versus hypertonic glucose alone Abel 1973 and Feinstein 1981 compared ELAA and hypertonic glucose. Abel 1973 reported recovery from AKI, survival on dialysis, average slope of SCr and BUN levels for ELAA versus glucose. Feinstein 1981 recorded urea nitrogen appearance, SCr and serum proteins concentration.
Allocation
Randomisation
Two studies (Abel 1973; Feinstein 1981) clearly described the use of a random number table to generate the allocation sequence. The other six studies (De Aguilar 1982; Feinstein 1983; Fiaccadori 2005; Martinez 1980; Mirtallo 1982; Singer 2007) mentioned randomly allocated but provided no further details.
Allocation concealment
None of the studies provided any information about allocation concealment.
Blinding Four studies were double-blind (Abel 1973; Feinstein 1981; Fiaccadori 2005; Mirtallo 1982), however only two of these described blinding in detail (Abel 1973; Feinstein 1981). Four studies did not mention blinding (De Aguilar 1982; Feinstein 1983; Martinez 1980; Singer 2007).
Recovery from AKI
Abel 1973 reported a statistically signicant recovery in patients treated with IV ELAA compared to glucose alone (Analysis 1.1.1: RR 1.70, 95% CI 1.04 to 2.79). Abel 1973 also reported no signicant difference in the recovery of patients with oliguric AKI treated with L-EAA compared to glucose alone (Analysis 1.1.2: RR 1.78, 95% CI 0.97 to 3.27).
Incomplete outcome data Six studies (Abel 1973; De Aguilar 1982; Feinstein 1981; Feinstein 1983; Martinez 1980; Singer 2007) did not describe withdrawals or drop-outs, however enrolled numbers and numbers reported for the outcomes were the same. Fiaccadori 2005 reported two patients were withdrawn from the analysis (death [1], serum triglycerides > 5.1 mmol/L [1]).Mirtallo 1982 reported ve patients discontinued because of suspected sepsis.No study used intentionto-treat.
Survival on dialysis
The percentage of patients who underwent dialysis if required was 53% (Abel 1973). Eleven of 17 patients who underwent dialysis survived in the ELAA group compared to 2/11 patients in the glucose alone group (Analysis 1.2: RR 3.56, 95% CI 0.97 to 13.08).
Average slope of SCr (mg/dL)
Selective reporting Six studies (De Aguilar 1982; Feinstein 1981; Feinstein 1983; Fiaccadori 2005; Martinez 1980; Singer 2007) reported all the measurements listed in their methods section. Abel 1973 did not list any planned measurements, therefore the reporting bias is unclear. Mirtallo 1982 did not report serum glucose and CO content.
Abel 1973 reported a signicant decrease in the average slope of SCr in the ELAA group compared to the glucose alone group (Analysis 1.3: MD -0.78 mg/dL, 95% CI -1.35 to -0.21).
Average slope of BUN (mg/dL)
Abel 1973 reported a signicant decrease the average slope of BUN in the ELAA group compared to the glucose alone group (Analysis 1.4: MD -11.10 mg/dL, 95% CI -19.68 to -2.52).
SCr (mg/dL)
Nitrogen metabolism
Feinstein 1981 showed no signicant difference between the two groups in SCr (Analysis 1.5: MD -0.70 mg/dL, 95% CI -4.05 to 2.65).
Serum proteins (g/dL)
There was no signicant difference between the EAA and GAA groups for estimated protein nitrogen balance (Analysis 3.2: MD 0.29 g/d, 95% CI -0.45 to 1.03) and signicant differences in urea nitrogen appearance (Analysis 3.3: MD 0.98 g/d, 95% CI 0.25 to 1.71) and net protein utilisation (Analysis 3.4: MD 21.50%, 95% CI 0.39 to 42.61).
Feinstein 1981 showed no signicant difference in serum protein concentrations between the ELAA and glucose group (Analysis 1.6: MD -0.40 g/dL, 95% CI -1.50 to 0.70).
High-dose AA versus normal-dose AA Singer 2007 reported BUN increased signicantly from baseline in normal-dose AA group (P < 0.04) but not in the high-dose AA group, while CrCl was not modied signicantly in either group. There was no signicant difference between groups in cumulative water excretion.
Urea nitrogen appearance (g/d)
Feinstein 1981 showed no signicant improvement in urea nitrogen appearance in the ELAA group compared to the glucose group (Analysis 1.7: MD -3.70 g/d, 95% CI -9.80 to 2.40).
Death
High ENAA nitrogen intake versus low EAA nitrogen intake Feinstein 1983 reported urea nitrogen appearance and estimated protein nitrogen balance for high ENAA versus low EAA nitrogen intake.
There was no statistical signicance in death between the two groups (Analysis 4.1: RR 1.13, 95% CI 0.27 to 4.76).
Haemodialysis requirement
There was no signicant difference in the requirement for haemodialysis between the two groups (Analysis 4.2: RR 1.67, 95% CI 0.17 to 12.94).
The appearance urea nitrogen was signicantly lower in the low EAA nitrogen group compared to the high ENAA nitrogen group (Analysis 2.1: MD 6.50 g/d, 95% CI 0.02 to 12.98).
Nitrogen balance (g/d)
Estimated protein nitrogen balance (g/d)
Daily nitrogen balance showed no signicant difference from baseline in normal-dose AA group, while there was a signicant increase in the high-dose AA group (P < 0.01). There was no signicant difference between the two groups for the cumulative nitrogen balance (Analysis 4.3: MD 13.40 g/d, 95% CI -1.37 to 28.17).
Protein nitrogen balance was estimated from the difference between nitrogen intake and urea nitrogen appearance and were negative in both groups. There was no statistical signicance (Analysis 2.2: MD 2.20 g/d, 95% CI -1.89 to 6.29).
Furosemide requirement (mg/d)
EAA versus GAA Mirtallo 1982 reported death and nitrogen metabolism (estimated protein nitrogen balance, urea nitrogen appearance and net protein utilisation) for EAA versus GAA.
Although there was no difference in water balance between the two groups, the high-dose AA group had a signicantly lower cumulative furosemide requirements than the normal-dose AA group (Analysis 4.4: MD -351.00 mg/d, 95% CI -658.13 to 43.87).
Glucose + EAA + histidin versus glucose + GAA Three studies (De Aguilar 1982; Feinstein 1981; Martinez 1980) compared glucose+EAA + histidin versus glucose + GAA. De Aguilar 1982 and Martinez 1980 reported nitrogen balance, plasma urea, U/P urea and SCr, and Feinstein 1981 reported SCr, urea nitrogen appearance and serum proteins.
10
Death
There was no signicant difference in death between the EAA and GAA groups (Analysis 3.1: RR 1.52, 95% CI 0.63 to 3.68).
Plasma urea (g/L)
There was signicant improvement in nitrogen balance for the glucose+EAA+histidin group than the glucose+GAA group (Analysis 5.1 (2 studies, 63 patients): MD -1.93 g/d, 95% CI -2.84 to 1.01).
Glucose + nitrogen + fat signicantly lowered plasma urea compared to glucose + EAA + histidin (Analysis 6.2 (2 studies, 58 patients): MD 0.40 g/L, 95% Cl 0.19 to 0.61).
U/P urea Plasma urea (g/L)
There was no signicant difference between the two groups in plasma urea (Analysis 5.2 (2 studies, 63 patients): MD 0.15 g/L, 95% CI -0.10 to 0.40).
Glucose + EAA + histidin signicantly lowered U/P urea compared to glucose + nitrogen + fat (Analysis 6.3 (2 studies, 58 patients): MD -5.12, 95% Cl -10.13 to -0.10).
U/P urea
SCr (mg/dL)
There was no signicant difference between the two groups in U/ P urea (Analysis 5.3 (2 studies, 63 patients): MD 0.90, 95% CI 4.65 to 6.46)
There was a signicant increase in SCr in the glucose + nitrogen + fat group compared with glucose + EAA + histidin group (Analysis 6.4 (2 studies, 58 patients): MD 0.42 mg/dL, 95% Cl 0.17 to 0.67).
SCr (mg/dL)
There was no signicant difference between the two groups for SCr (Analysis 5.4 (3 studies, 86 patients): MD 0.07 mg/dL, 95% CI -0.23 to 0.37).
Glucose+GAA versus glucose+nitrogen+fat Two studies (De Aguilar 1982; Martinez 1980) compared glucose + GAA versus glucose + nitrogen + fat and reported nitrogen balance, plasma urea, U/P urea and SCr.
Feinstein 1981 reported a signicant difference in improvement of urea nitrogen appearance between the EAA group and GAA group (Analysis 5.5: MD -7.30 g/d, 95% CI -13.51 to -1.09). GAA group resulted better urea nitrogen appearance compared to EAA group.
There was no signicant difference between the two groups for nitrogen balance (Analysis 7.1 (2 studies, 67 patients): MD -0.21 g/d, 95% -0.74 to 0.33).
Plasma urea (g/L) Serum proteins (g/dL)
Feinstein 1981 reported no signicant difference in serum protein concentration between the EAA group and GAA group (Analysis 5.6: MD 0.70 g/dL, 95% CI -0.07 to 1.47).
There was no signicant difference between the two groups for plasma urea (Analysis 7.2 (2 studies, 67 patients): MD 0.25 g/L, 95% Cl -0.26 to 0.76).
Glucose + EAA + histidin versus glucose+nitrogen+fat Two studies (De Aguilar 1982; Martinez 1980) compared glucose + EAA + histidin versus glucose+nitrogen+fat and reported nitrogen balance, plasma urea, U/P urea and SCr.
U/P urea
Glucose + GAA signicantly lowered U/P urea compared to glucose+nitrogen+fat (Analysis 7.3 (2 studies, 67 patients): MD 6.02, 95% CI -11.63 to -0.40).
Nitrogen balance (g/dL)
SCr (mg/dL)
Glucose + EAA + histidin signicantly improved nitrogen balance compared to glucose+nitrogen+fat (Analysis 6.1 (2 studies, 58 patients): MD -2.13 g/dL, 95% CI -2.97 to -1.29).
There was a signicant increase in SCr in the glucose+nitrogen+fat group compared with glucose+GAA group (Analysis 7.4 (2 studies, 67 patients): MD 0.32 mg/dL, 95% CI 0.13 to 0.52).
11
Higher calorie-TPN versus lower calorie-TPN Fiaccadori 2005 excluded two patients from the analysis (death (1), serum triglycerides > 5.1 mmol/L (1)). Compared with the lower calorie-TPN, the higher calorie-TPN regimen did not improve estimated nitrogen balance (1.55 g/d, 95% CI -0.95 to 4.05; P = 0.18), protein catabolic rate (-0.10 g/kg/d, 95% CI -0.33 to 0.14; P = 0.35), or urea generation rate (-1.3 mg/min, 95% CI -5.2 to 2.7; P = 0.46), whereas it increased serum triglycerides (1.36 mmol/L, 95% CI 0.53 to 2.19; P = 0.007), glucose (1.15 mmol/L, 95% CI 0.07 to 2.24; P = 0.041), insulin need (20.4 U/d, 95% CI 8.3 to 32.6; P = 0.006) and nutritional uid administration (468 mL/d, 95% CI 370 to 566; P < 0.001). The paper didnt provide means or standard deviations and we were unable to meta-analyse the data. Adverse effects Abel 1973 reported one complication related to catheter insertion, and three instances of septicaemia which cleared on removal and relocation of the infusion catheter. Abel 1973 and Fiaccadori 2005 mentioned the risks of overfeeding patients with calories including hyperglycaemia which may lead to infection and nonketotic coma which was controlled by the use of insulin. Abel 1973 reported that there were no signicant differences in the frequency of hyperglycaemia between the two groups. Fiaccadori 2005 suggested higher calorie-TPN may increase the risk of articial nutrition-related side-effects compared to lower calorie-TPN. Mirtallo 1982 reported three patients receiving EAA had severe glucose intolerance. Feinstein 1983 and Feinstein 1981 did not report adverse effects. None of the studies provided data on adverse effects that were suitable for statistical analysis.
nitrogen and low EAA nitrogen, but no difference in estimated protein nitrogen balance. High-dose AA did not improve nitrogen balance, death or haemodialysis requirement, but there was significant decrease in furosemide requirement between high-dose AA and normal-dose AA. Glucose + EAA + histidin signicantly improved nitrogen balance compared with glucose+GAA and glucose + nitrogen + fat; glucose + nitrogen + fat signicantly improved SCr compared to EAA and GAA. Compared with the lower calorie-TPN, the higher calorie-TPN regimen did not improve estimated nitrogen balance, protein catabolic rate, or urea generation rate, whereas it increased serum triglycerides, glucose, insulin need and nutritional uid administration.
Overall completeness and applicability of evidence

Two studies (Feinstein 1983; Mirtallo 1982) compared EAA with ENAA or GAA. The outcomes measured were the same (urea nitrogen appearance and estimated protein balance), however the doses were quite different in the ENAA group. Nitrogen was 2.2 g in the ENAA group in Mirtallo 1982 and 11.3 g in Feinstein 1983. Three studies (De Aguilar 1982; Feinstein 1981; Martinez 1980) compared EAA and histidin with GAA. Only SCr was reported in all three studies. De Aguilar 1982 and Martinez 1980 reported nitrogen balance, plasma urea, U/P urea, while Feinstein 1981 reported urea nitrogen appearance, serum proteins. Since most interventions and outcome measures were different for each study, we were only able to perform a few combined analyses. A similar problem occurred when subgroup analysis was attempted for Fiaccadori 2005 and Singer 2007. Both studies were carried out in critically ill patients in the ICU, however Fiaccadori 2005 compared different energy intakes and Singer 2007 compared high versus normal AA. Only two studies reported mortality (Mirtallo 1982; Singer 2007). Six studies (De Aguilar 1982; Feinstein 1981; Feinstein 1983; Fiaccadori 2005; Martinez 1980; Mirtallo 1982) used urea nitrogen appearance and/or estimated protein balance as the measurements, and Mirtallo 1982 also used net protein utilisation to evaluate the nitrogen metabolism. Abel 1973 used recovery from AKI and average slope of SCr/BUN level as the measures of kidney function. Fiaccadori 2005 also measured serum triglycerides and glucose. We recommend future clinical studies use accredited and standard outcome measures in order to facilitate data analysis and conserve health resources. The unclear results reported have also brought difculties to the analysis. Fiaccadori 2005 reported results in scatter plots without exact data, and only give the average estimated nitrogen balance, protein catabolic rate, urea generation rate, with no standard deviations making meta-analysis impossible. None of the studies reported types of adverse effects, number of patients with complications, severity of adverse effects and the relevant treatment.
12
DISCUSSION
Summary of main results

ELAA signicantly improved survival on dialysis, average slope of SCr level and BUN level, but there was no improvement in recovery from AKI, SCr, serum protein concentration or urea nitrogen appearance compared with hypertonic glucose. Compared to EAA, GAA signicantly improved urea nitrogen appearance and net protein utilisation, but there was no signicant improvement in death or estimated protein nitrogen balance. There was a signicant difference in urea nitrogen balance between high ENAA
Quality of the evidence

We found the studies analysed were of poor quality. Although the studies used randomised allocation, only Abel 1973 and Feinstein 1981 described how the randomisation was performed but none described allocation concealment. Four studies used double-blinding. Abel 1973 and Feinstein 1981 clearly described double-blinding, while two just mentioned the method without any further details (Fiaccadori 2005; Mirtallo 1982). The remaining four studies did not mention blinding. Fiaccadori 2005 and Mirtallo 1982 described the number of withdrawals and drop-outs, and we were able to calculate the withdrawal and drop-out numbers for Abel 1973. The other ve studies did not describe withdrawals or dropouts. While AKI is not a chronic disease, and there is generally no need to follow-up, studies should report the number of patients who need long-term haemodialysis for those with low or no recovery of kidney function.
from nutritional treatment and survival has yet to be established (Sponsel 1995). Considering complications such as electrolyte and lipid imbalance, which is consistent with the outcomes of Fiaccadori 2005, Sponsel 1995 suggested nutrition therapy should be based on the estimated metabolic stress and protein-energy requirements of the individual AKI patients. Enteric nutrition has become more and more important in recent years (Druml 2001). Despite the difculty in demonstrating clear-cut benets of nutrition therapy, there is no doubt that nutritional treatment is important in the treatment of patients with AKI. Naylor 1987 performed a meta-analysis to evaluate the effectiveness of EAA, GAA and hypertonic glucose. Although the data suggested that EAA may show benets compared to GAA and hypertonic glucose alone, the efcacy of these parenteral nutritional therapies remains uncertain.
Potential biases in the review process

The poor methodological quality of the studies may result in bias. For example, the difference in age in one study (Singer 2007) may have inuence on the baseline comparability. This may impact on the results, since patients in the high-dose AA group were significant older than patients in normal-dose group (P < 0.05). No or inadequate allocation concealment may increase the risk of selection bias since participants may be included in the group the investigators think would be benecial.
AUTHORS CONCLUSIONS Implications for practice

There is no strong evidence to conclude that ELAA, high calorieTPN, high-dose amino acids or nitrogen and fat improves the survival and recovery from AKI in critically ill patients.
Implications for research

More high quality clinical studies are required for assessing the effects of different nutritional supplements. Randomisation and methods of allocation concealment should be fully described to assist in the assessment of potential risk of bias. Studies should report the withdrawal and drop-out rates in order to judge sufcient sample available to analysis. Adverse effect should be reported in detail including the severity and numbers in each group. Studies should use accredited standard outcome measures which make combined analyses possible. These outcomes should include mortality, participants perceived quality of life, length of hospital stay and the need for ongoing dialysis.
Agreements and disagreements with other studies or reviews

Nutrition therapy for AKI has been studied for more than half century. After Abel 1973, there has been several studies evaluating efciency and safety of nutrition therapy for AKI. Leonard 1975 found no change in recovery of kidney function in EAA group compared with controlled group, unlike Abel 1973 which reported EAA appeared to hasten kidney function recovery. Other studies focused on the comparison between GAA and EAA. A non-randomised study by Freund 1980 compared parenteral nutrition using GAA with EAA data from Abel 1973. They reported a signicantly lower survival rate (9%) in the GAA group compared to the EAA group (75%), which was the reverse of the results of Mirtallo 1982. Blumenkrantz 1978 reported no signicant difference between EAA (21 g/d) and GAA (42 g/d) in serum urea nitrogen levels, serum urea nitrogen/creatinine ratios or urea appearance rates. The value of nutritional treatment for AKI has been debated because of the concerns with the complications of parental nutrition therapy, and the relationship between changes in metabolism
ACKNOWLEDGEMENTS
We would like to thank: Narelle Willis and Ruth Mitchell (Cochrane Renal Group) for their help during the preparation of this review Pamela Lopez-Vargas for translation of the Spanish papers The referees for their editorial advice during the preparation of this review.
13
REFERENCES
References to studies included in this review

Abel 1973 {published data only} Abel RM, Beck CH Jr, Abbott WM, Ryan JA Jr, Barnett GO, Fischer JE. Improved survival from acute renal failure after treatment with intravenous essential L-amino acids and glucose. Results of a prospective, double-blind study. New England Journal of Medicine 1973;288(14):6959. [MEDLINE: 4631743] De Aguilar 1982 {published data only} Capparros Fernandez de Aguilar T, Lopez Martinez J, Perez Picouto F. Parenteral nutrition and hypermetabolic acute renal failure. Revista Clinica Espanola 1982;165(4):23944. [MEDLINE: 6813921] Feinstein 1981 {published data only} Feinstein EI, Blumenkrantz MJ, Healy M, Kofer A, Silberman H, Massry SG, et al.Clinical and metabolic responses to parenteral nutrition in acute renal failure. A controlled double-blind study. Medicine 1981;60(2): 12437. [MEDLINE: 6783809] Feinstein 1983 {published data only} Feinstein EI, Kopple JD. Silberman H. Massry SG. Total parenteral nutrition with high or low nitrogen intakes in patients with acute renal failure. Kidney InternationalSupplement 1983;16:S31923. [MEDLINE: 6429406] Fiaccadori 2005 {published data only} Fiaccadori E, Maggiore U, Rotelli C, Giacosa R, Picetti E, Parenti E, et al.Effects of different energy intakes on nitrogen balance in patients with acute renal failure: a pilot study. Nephrology Dialysis Transplantation 2005;20(9): 197680. [MEDLINE: 15998652] Fiaccadori E, Rotelli F, Giacosa R, Picetti E, Maccari C, Maggiore U, et al.Energy intake and nitrogen balance in acute renal failure. [abstract no: SU-PO234]. Journal of the American Society of Nephrology 2004;15(Oct):583A. Martinez 1980 {published data only} Lopez Martinez J, Caparros T, Perez Picouto F, Lopez Diez F, Cereijo E. Parenteral nutrition in septic patients with acute renal failure in polyuric phase. Revista Clinica Espanola 1980;157(3):1717. [MEDLINE: 6773113] Mirtallo 1982 {published data only} Mirtallo JM, Schneider PJ, Mavko K, Ruberg RL, Fabri PJ. A comparison of essential and general amino acid infusions in the nutritional support of patients with compromised renal function. Jpen: Journal of Parenteral & Enteral Nutrition 1982;6(2):10913. [MEDLINE: 6808169] Singer 2007 {published data only} Singer P. High-dose amino acid infusion preserves diuresis and improves nitrogen balance in non-oliguric acute renal failure. Wiener Klinische Wochenschrift 2007;119(7-8): 21832. [MEDLINE: 17492348]
Baek 1975 {published data only} Baek SM, Makabali GG, Bryan-Brown CW, Kusek J, Shoemaker WC. The inuence of parenteral nutrition on the course of acute renal failure. Surgery, Gynecology & Obstetrics 1975;14(3):4058. [MEDLINE: 808871] Berg 2007 {published data only} Berg A, Norberg A, Martling CR, Gamrin L, Rooyackers O, Wernerman J. Glutamine kinetics during intravenous glutamine supplementation in ICU patients on continuous renal replacement therapy. Intensive Care Medicine 2007 Apr;33(4):6606. [MEDLINE: 17318498] Berger 2008 {published data only} Berger MM, Soguel L, Shenkin A, Revelly JP, Pinget C, Baines M, Chiolero RL. Inuence of early antioxidant supplements on clinical evolution and organ function in critically ill cardiac surgery, major trauma, and subarachnoid hemorrhage patients. Critical Care 2008;12(4):R101. [EMBASE: 2008411873] Blumenkrantz 1978 {published data only} Blumenkrantz MJ, Kopple JD, Kofer A, Kamdar AK, Healy MD, Feinstein EI, et al.Total parenteral nutrition in the management of acute renal failure. American Journal of Clinical Nutrition 1978;31(10):183140. [MEDLINE: 101071] Gjorup 1958 {published data only} Gjorup S. Protein-sparing action of glucose administered intracavally in patients with acute renal failure. Acta Medica Scandinavica 1958;161(3):23341. Leonard 1975 {published data only} Leonard CD, Luke RG, Siegel RR. Parenteral essential amino acids in acute renal failure. Urology 1975;6(2): 1547. [MEDLINE: 807007] Lopez Martinez 1988 {published data only} Lpez Martinez J, Castrillo Garcia JM, Rapado Errasti A, Perez Picouto F, Caparros Fernandez de Aguilar T. Hypomagnesemia in acute non-oliguric renal failure treated with parenteral nutrition. A study of its mechanisms. Revista Clnica Espaola 1988;183(6):28995. Mocan 1995 {published data only} Mocan MZ, Mocan H, Gacar MN, Ozgur GK, Uluutku MH. Effect of essential amino acid supplementation in acute renal failure. International Urology & Nephrology 1995;27(4):50310. [MEDLINE: 8586527] Proietti 1978 {published data only} Proietti R, Pelosi G, Scrascia E, Magalini SI, Bondoli A. Acute renal failure: biochemical evaluation of total parenteral nutrition with essential L-amino acids. Resuscitation 1978;6(3):1916. [MEDLINE: 105386] Smolle 1997 {published data only} Smolle KH, Kaufmann P, Fleck S, Lueger A, Mausser G, Polz W, et al.Inuence of a novel amino acid solution (enriched with the dipeptide glycyl-tyrosine) on plasma amino acid concentration of patients with acute renal
14
References to studies excluded from this review
failure. Clinical Nutrition 1997;16(5):23946. [EMBASE: 1998017394]
Additional references
Anderson 1980 Anderson RJ, Schrier RW. Acute renal failure. In: Stein JH editor(s) editor(s). Nephrology. Vol. 6, New York: Grune & Stratton, 1980. Berger 2004 Berger MM, Shenkin A, Revelly JP, Roberts E, Cayeux MC, Baines M, et al.Copper, selenium, zinc, and thiamine balances during continuous venovenous hemodialtration in critically ill patients. American Journal of Clinical Nutrition 2004;80(2):4106. [MEDLINE: 15277163] Druml 1998 Druml W, Schwarzenhofer M, Apsner R, Horl WH. Fatsoluble vitamins in patients with acute renal failure. Mineral & Electrolyte Metabolism 1998;24(4):2206. [MEDLINE: 9554560] Druml 2001 Druml W. Nutrition management of acute renal failure. American Journal of Kidney Diseases 2001;37(1 Suppl 2): S8994. [MEDLINE: 11158869] Feest 1993 Feest TG, Round A, Hamad S. Incidence of severe acute renal failure in adults: results of a community based study. BMJ 1993;306(6876):4813. [MEDLINE: 8448456] Fiaccadori 1999 Fiaccadori E, Lombardi M, Leonardi S, Rotelli CF, Tortorella G, Borghetti A. Prevalence and clinical outcome associated with preexisting malnutrition in acute renal failure: a prospective cohort study. Journal of the American Society of Nephrology 1999;10(3):58193. [MEDLINE: 10073609] Finn 1993 Finn WF. Recovery from acute renal failure. In: Lazarus JM, Brenner BM editor(s). Acute renal failure. 3. New York: Churchill Livingstone, 1993:55396. [: ISBN: 044308792X] Fouque 1998 Fouque D. Growth factors: future prospects in renal failure. Mineral & Electrolyte Metabolism 1998;24(1):2733. [MEDLINE: 9397414] Freund 1980 Freund H, Atamian S, Fischer JE. Comparative study of parenteral nutrition in renal failure using essential and nonessential amino acid containing solutions. Surgery, Gynecology & Obstetrics 1980;151(5):65256. [MEDLINE: 6776642] Higgins 2011 Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
Hou 1983 Hou SH, Bushinsky DA, Wish JB, Cohen JJ, Harrington JT. Hospital-acquired renal insufciency: a prospective study. American Journal of Medicine 1983;74(2):2438. [MEDLINE: 6824004] Koretz 2001 Koretz RL, Lipman TO, Klein S. AGA technical review on parenteral nutrition. Gastroenterology 2001;121(4): 9701001. [MEDLINE: 11606512] Koretz 2007 Koretz RL, Avenell A, Lipman TO, Braunschweig CL, Milne AC. Does enteral nutrition affect clinical outcome? A systematic review of the randomized trials. American Journal of Gastroenterology 2007;102(2):41229. [MEDLINE: 17311654] Naylor 1987 Naylor CD, Detsky AS, ORourke K, Fonberg E. Does treatment with essential amino acids and hypertonic glucose improve survival in acute renal failure?: A meta-analysis. Renal Failure 198788;10(3-4):14152. [MEDLINE: 3141988] Novak 1997 Novak I, Sramek V, Pittrova H, Rusavy P, Lacigova S, Eiselt M, et al.Glutamine and other amino acid losses during continuous venovenous hemodialtration. Articial Organs 1997;21(5):35963. [MEDLINE: 9129766] Santacruz 1996 Santacruz F, Barreto S, Mayor MM, Cabrera W, Breuer N. Mortality in elderly patients with acute renal failure. Renal Failure 1996;18(4):6015. [MEDLINE: 8875685] Schif 1994 Schif H, Lang SM, Konig A, Strasser T, Haider MC, Held E. Biocompatible membranes in acute renal failure: prospective case-controlled study. Lancet 1994;344(8922): 57073. [MEDLINE: 7914959] Sponsel 1995 Sponsel H, Conger JD. Is parenteral nutrition therapy of value in acute renal failure patients?. American Journal of Kidney Diseases 1995;25(1):96102. [MEDLINE: 7810542] Spreiter 1980 Spreiter SC, Myers BD, Swenson RS. Protein-energy requirements in subjects with acute renal failure receiving intermittent hemodialysis. American Journal of Clinical Nutrition 1980;33(7):14337. [MEDLINE: 6772006] Thadhani 1996 Thadhani R, Pascual M, Bonventre JV. Acute renal failure. New England Journal of Medicine 1996;334(22):144860. [MEDLINE: 8618585] Toback 1983 Toback FG, Dodd RC, Maier ER, Havener LJ. Amino acid administration enhances renal protein metabolism after acute tubular necrosis. Nephron 1983;33(4):23843. [MEDLINE: 6843754]
15
Wolfson 1993 Wolfson M, Kopple JD. Nutritional management of acute renal failure. In: Lazarus MJ, Brenner BM editor(s). Acute renal failure. 3. New York: Churchill Livingstone, 1993: 46785. [: ISBN: 044308792X]
References to other published versions of this review

Li 2010 Li Y, Tang X, Zhang J, Wu T. Nutritional support for acute kidney injury. Cochrane Database of Systematic Reviews 2010, Issue 1. [DOI: 10.1002/14651858.CD005426.pub2] Wu 2005 Wu T, Li Y, Tang X, Zhang J. Nutritional support for acute renal failure. Cochrane Database of Systematic Reviews 2005, Issue 3. [DOI: 10.1002/14651858.CD005426] Indicates the major publication for the study
16
CHARACTERISTICS OF STUDIES
Characteristics of included studies [ordered by study ID]

Abel 1973 Methods Study design: Prospective, double-blind, RCT Setting: Hyperalimention Unit, Massachusetts General Hospital Adult participants who had sustained a presumed renal insult within 10 days before inclusion Number (treatment/control): 53 (28/25) Treatment group ELAA Control group Hypertonic glucose Infusion rates in both group were 30 to 75 mL/h for 15 days All participants might go on dialysis if required Recovery from kidney failure Survival on dialysis Average slope of SCr level (mg/dL) Average slope of BUN level (mg/dL)
Participants
Interventions
Outcomes
Notes
Supported in part by a research grant to the Laboratory of Computer Sciences and a grant to the Renal Unit. Analyses were performed with the use of the MUMPS programming language. There were no detailed data on complications.
Risk of bias Bias Authors judgement Support for judgement Random number table
Random sequence generation (selection Low risk bias) Allocation concealment (selection bias) Unclear risk
Not stated Quote:patients assigned a code number and solution based on a randomized sequence know only to members of the pharmacy Not stated
Blinding (performance bias and detection Low risk bias) All outcomes
Blinding of outcome assessment (detection Unclear risk bias) All outcomes Incomplete outcome data (attrition bias) All outcomes Low risk
No patients missing from either group
17
Abel 1973
(Continued)
Selective reporting (reporting bias) Other bias De Aguilar 1982 Methods
Unclear risk Low risk
No measurements listed in methods No conict of interest
Study design: RCT Setting: Servicio de Madicina Intensiva (UVI) Patients aged between 16 and 61 in acute kidney failure by gram negative bacteria were included Number (group 1/group 2/group 3): 59 (17/23/19) Group 1 ELAA, L-histidin and 2000 kcal/d with glucose. Group 2 10 g of nitrogen consisting of a mixture of EAA and NEAA and 3000 kcal/d exclusively with glucose. Group 3 10 g nitrogen consisting of a mixture of EAA and NEAA and 3000 kcal/d of which 1000 kcal was contributed by lipids (intralipid 10%). Plasma urea U/P urea SCr Nitrogen balance
Participants
Interventions
Outcomes
Notes Risk of bias Bias
The statistical analysis used was a t-test of matched data.
Authors judgement
Support for judgement Not stated
Random sequence generation (selection Unclear risk bias) Allocation concealment (selection bias) Unclear risk
Not stated Not stated
Blinding (performance bias and detection Unclear risk bias) All outcomes Blinding of outcome assessment (detection Unclear risk bias) All outcomes Incomplete outcome data (attrition bias) All outcomes Low risk
Not stated

18
De Aguilar 1982
(Continued)
Selective reporting (reporting bias)
Low risk
Measurements listed in methods were all reported No conict of interest
Other bias Feinstein 1981 Methods
Low risk
Study design: Prospective double-blind RCT Setting: Division of Nephrology and Departments of Medicine and Surgery, The University of Southern California Medical Center and the Medical and Research Services of the Veterans Administration Wadsworth Medical Center and the Schools of Medicine and Public Health, UCLA Center for the Health Sciences, LA, California Participants with AKI Number (treatment/control): 30 (7/11/12) Sex (M/F): 29/1 Group 1 Hypertonic dextrose Group 2 Dextrose and 21 g EAA Group 3 Dextrose and 21.2 g EAA and 20.9 g NEAA SCr Urea nitrogen appearance Serum protein Plasma amino acid
Participants
Interventions
Outcomes
Notes
Statistical analyses were performed using Students test, the paired t-test, the chi square test, linear regression analysis, and the Fisher exact probability test.
Risk of bias Bias Authors judgement Support for judgement Random numbers at USC-LACMC
Random sequence generation (selection Low risk bias) Allocation concealment (selection bias) Unclear risk
Not stated The randomised group was known only to members of the pharmacy and the solutions used in both groups appeared the same Not stated
Blinding (performance bias and detection Low risk bias) All outcomes Blinding of outcome assessment (detection Unclear risk bias) All outcomes
19
Feinstein 1981
(Continued)
Incomplete outcome data (attrition bias) All outcomes Selective reporting (reporting bias)
Low risk
Low risk
Outcome measurements listed in methods were all reported No conict of interest
Other bias Feinstein 1983 Methods
Low risk
Study design: Prospective RCT Setting: Los Angeles County-University of Southern California Medical Center Participants with AKI Number (treatment/control): 11 (6/5) Sex (M/F): 10/1 Treatment group EAA and NEAA Control group EAA Urea nitrogen appearance Protein nitrogen balance Statistical analyses were performed using Students test for the independent and non-independent means.
Participants
Interventions
Outcomes
Notes
Risk of bias Bias Authors judgement Support for judgement Not stated
Blinding (performance bias and detection Unclear risk bias) All outcomes Blinding of outcome assessment (detection Unclear risk bias) All outcomes Incomplete outcome data (attrition bias) All outcomes Low risk
Not stated
20
Feinstein 1983
(Continued)
Low risk
Measurements listed in methods were all reported No conict of interest
Other bias Fiaccadori 2005 Methods
Low risk
Study design: Prospective, crossover, open-label RCT Setting: Dipartimento di Clinica Medica, Nefrologia and Scienze della Prevenzione, Universita degli Studi di Parma, Italy Participants with AKI Number (group 1/group 2): 10 (5/5) Group 1 Higher calorie-lower calorie TPN sequence Group 2 Lower calorie-higher calorie TPN sequence Nitrogen balance Protein catabolic rate Urea generation rate (mg/min) Triglycerides (mmol/L) Glucose (mmol/L) Insulin use (U/d) Volume (mL/d)
Participants
Interventions
Outcomes
All analyses were performed using the statistical package GenStat release 7.2.
Authors judgement
Not stated Stated double-blind, no further details provided
Blinding (performance bias and detection Unclear risk bias) All outcomes Blinding of outcome assessment (detection Unclear risk bias) All outcomes
Not stated
21
Fiaccadori 2005
(Continued)
Incomplete outcome data (attrition bias) All outcomes
High risk
2 patients were withdrawn from the analysis (1 due to death, 1due to serum triglycerides > 5.1 mmol/L) Measurements listed in methods were all reported No conict of interest
Low risk
Other bias Martinez 1980 Methods
Low risk
Study design: RCT Setting: Unidad de Vigilancia Intensiva Adult patients with AKI in polyuria phase during a bacteraemia episode Number (group 1/group 2/group 3): 35 (10/13/12) Group 1 2000 kcal in the form of glucose and 4.38 g/d of nitrogen with EAA + histidin. Total volume 3000 mL. Group 2 3000 kcal with glucose and 15 g/d of nitrogen with EAA and L-NEAA and with a AAE/AAT ratio of 0.5 (nitrogen 15). Total volume 3000 mL. Group 3 A daily dose of 15 g of nitrogen, 3000 kcal provided by 500 g of glucose and 100 g of fat (intralipid 10%). Nitrogen balance Urea plasma U/P urea SCr
Participants
Interventions
Outcomes
Notes
The comparative study between the different groups we used means of the test of Gosset-Student.
Blinding (performance bias and detection Unclear risk bias) All outcomes
22
Martinez 1980
(Continued)
Blinding of outcome assessment (detection Unclear risk bias) All outcomes Incomplete outcome data (attrition bias) All outcomes Selective reporting (reporting bias) Low risk
Not stated
Low risk
Outcome measurements listed in methods were all reported Other bias is unclear
Other bias Mirtallo 1982 Methods
Low risk
Study design: Prospective RCT Setting: General Medicine and Surgical Units of The Ohio State University Hospitals Number: 45 AKI (41), CKD with superimposed acute illness (2 in each group) Treatment group General AA Control group EAA Mortality rate Nitrogen metabolism Estimated nitrogen balance Urea nitrogen appearance Net protein utilisation Electrolyte balance Serum potassium Serum magnesium
Participants
Interventions
Outcomes
Differences between groups were evaluated by Student unpaired t-test.
Authors judgement
Unclear
23
Mirtallo 1982
(Continued)
Blinding (performance bias and detection Unclear risk bias) All outcomes Blinding of outcome assessment (detection Unclear risk bias) All outcomes Incomplete outcome data (attrition bias) All outcomes High risk
Stated double-blind, no further details provided
Not stated
5/45 (2/21 from GAA group; 3/24 from EAA group) discontinued due to suspected sepsis Serum glucose and CO2 content listed in methods were not reported No conict of interest
High risk
Other bias Singer 2007 Methods
Low risk
Study design: Prospective RCT Setting: Department of General Intensive Care, Rabin Medical Center, and the Sackler School of Medicine, Tel Aviv University Critically ill patients with AKI Number (group 1/group 2): 14 (6/8) Group 1 Normal-dose AA Group 2 High-dose AA Furosemide Nitrogen balance Death Statistical analysis dened the necessary number of patients. Students t-test was used to compare the two groups and a multiple ANOVA tested variations between days.
Participants
Interventions
Outcomes
Notes
Unclear
24
Singer 2007
(Continued)
Blinding (performance bias and detection Unclear risk bias) All outcomes Blinding of outcome assessment (detection Unclear risk bias) All outcomes Incomplete outcome data (attrition bias) All outcomes Selective reporting (reporting bias) Low risk
Not stated
Not stated
Low risk
Outcome measurements listed in methods were all reported No conict of interest
Other bias
Low risk
AA - amino acids; AKI - acute kidney injury; BUN - blood urea nitrogen; CKD - chronic kidney disease; EAA - essential AA; ELAA essential L-AA; NEAA - nonessential AA; SCr - serum creatinine; TPN - total parenteral nutrition
Characteristics of excluded studies [ordered by study ID]
Study Baek 1975 Berg 2007 Berger 2008 Blumenkrantz 1978 Gjorup 1958 Leonard 1975 Lopez Martinez 1988 Mocan 1995 Proietti 1978 Smolle 1997
Reason for exclusion Not RCT Wrong population Wrong population The values of outcomes were marked in the gures, but no exact data given in the text Not RCT Single blind-controlled clinical study, but no randomised allocation Not RCT Not RCT Single blind-controlled clinical study, but no randomised allocation Double-blind RCT but aimed to test plasma AA concentration unrelated to kidney function
AA: amino acids

Nutritional support for acute kidney injury (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 25
DATA AND ANALYSES
Comparison 1. Essential L-amino acids (ELAA) versus glucose
Outcome or subgroup title 1 Recovery from acute kidney injury 1.1 All patients 1.2 Oliguric patients 2 Survival on dialysis 3 Average slope of serum creatinine 4 Average slope of blood urea nitrogen 5 Serum creatinine 6 Serum proteins 7 Urea nitrogen appearance
No. of studies 1 1 1 1 1 1 1 1 1
No. of participants
Statistical method Risk Ratio (M-H, Random, 95% CI) Risk Ratio (M-H, Random, 95% CI) Risk Ratio (M-H, Random, 95% CI) Risk Ratio (M-H, Random, 95% CI) Mean Difference (IV, Random, 95% CI) Mean Difference (IV, Random, 95% CI) Mean Difference (IV, Random, 95% CI) Mean Difference (IV, Random, 95% CI) Mean Difference (IV, Random, 95% CI)
Effect size Totals not selected 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] Totals not selected Totals not selected Totals not selected Totals not selected Totals not selected Totals not selected
Comparison 2. High essential and nonessential amino acid (ENAA) nitrogen intake versus low essential amino acid (EAA) nitrogen intake
Outcome or subgroup title 1 Urea nitrogen appearance 2 Estimated protein nitrogen balance
No. of studies 1 1
No. of participants
Statistical method Mean Difference (IV, Random, 95% CI) Mean Difference (IV, Random, 95% CI)
Effect size Totals not selected Totals not selected
Comparison 3. Essential amino acids (EAA) versus general amino acids (GAA)
Outcome or subgroup title 1 Death 2 Estimated protein nitrogen balance 3 Urea nitrogen appearance 4 Net protein utilisation
No. of studies 1 1 1 1
No. of participants
Statistical method Risk Ratio (M-H, Random, 95% CI) Mean Difference (IV, Random, 95% CI) Mean Difference (IV, Random, 95% CI) Mean Difference (IV, Random, 95% CI)
Effect size Totals not selected Totals not selected Totals not selected Totals not selected
26
Comparison 4. High-dose amino acids (AA) versus normal-dose AA
Outcome or subgroup title 1 Death 2 Haemodialysis requirement 3 Cumulative nitrogen balance 4 Furosemide requirement
No. of participants
Statistical method Risk Ratio (M-H, Random, 95% CI) Risk Ratio (M-H, Random, 95% CI) Mean Difference (IV, Random, 95% CI) Mean Difference (IV, Random, 95% CI)
Effect size Totals not selected Totals not selected Totals not selected Totals not selected
Comparison 5. Glucose+EAA+histidin versus glucose+GAA
Outcome or subgroup title 1 Nitrogen balance 2 Plasma urea 3 U/P urea 4 Serum creatinine 5 Urea nitrogen appearance 6 Serum proteins
No. of studies 2 2 2 3 1 1
No. of participants 63 63 63 86
Statistical method Mean Difference (IV, Random, 95% CI) Mean Difference (IV, Random, 95% CI) Mean Difference (IV, Random, 95% CI) Mean Difference (IV, Random, 95% CI) Mean Difference (IV, Random, 95% CI) Mean Difference (IV, Random, 95% CI)
Effect size -1.93 [-2.84, -1.01] 0.15 [-0.10, 0.40] 0.90 [-4.65, 6.46] 0.07 [-0.23, 0.37] Totals not selected Totals not selected
Comparison 6. Glucose+EAA+histidin versus glucose+nitrogen+fat
Outcome or subgroup title 1 Nitrogen balance 2 Plasma urea 3 U/P urea 4 Serum creatinine
Statistical method Mean Difference (IV, Random, 95% CI) Mean Difference (IV, Random, 95% CI) Mean Difference (IV, Random, 95% CI) Mean Difference (IV, Random, 95% CI)
Effect size -2.13 [-2.97, -1.29] 0.4 [0.19, 0.61] -5.12 [-10.13, -0.10] 0.42 [0.17, 0.67]
Comparison 7. Glucose+GAA versus glucose+nitrogen+fat
Outcome or subgroup title 1 Nitrogen balance 2 Plasma urea 3 U/P urea 4 Serum creatinine
Statistical method Mean Difference (IV, Random, 95% CI) Mean Difference (IV, Random, 95% CI) Mean Difference (IV, Random, 95% CI) Mean Difference (IV, Random, 95% CI)
Effect size -0.21 [-0.74, 0.33] 0.25 [-0.26, 0.76] -6.02 [-11.63, -0.40] 0.32 [0.13, 0.52]
27
Analysis 1.1. Comparison 1 Essential L-amino acids (ELAA) versus glucose, Outcome 1 Recovery from acute kidney injury.
Review: Nutritional support for acute kidney injury
Comparison: 1 Essential L-amino acids (ELAA) versus glucose Outcome: 1 Recovery from acute kidney injury
Study or subgroup
ELAA n/N
Glucose n/N
Risk Ratio MH,Random,95% CI
1 All patients Abel 1973 2 Oliguric patients Abel 1973 14/18 7/16 1.78 [ 0.97, 3.27 ] 21/28 11/25 1.70 [ 1.04, 2.79 ]
0.2
0.5
Favours ELAA
Favours glucose
Analysis 1.2. Comparison 1 Essential L-amino acids (ELAA) versus glucose, Outcome 2 Survival on dialysis.
Comparison: 1 Essential L-amino acids (ELAA) versus glucose Outcome: 2 Survival on dialysis
Study or subgroup
ELAA n/N
Glucose n/N 2/11
Risk Ratio MH,Random,95% CI 3.56 [ 0.97, 13.08 ]
Abel 1973
11/17
0.05
0.2
20
Favours ELAA
Favours glucose
28
Analysis 1.3. Comparison 1 Essential L-amino acids (ELAA) versus glucose, Outcome 3 Average slope of serum creatinine.
Comparison: 1 Essential L-amino acids (ELAA) versus glucose Outcome: 3 Average slope of serum creatinine
Study or subgroup
ELAA N Mean(SD)[mg/dL] -0.28 (0.35)
Glucose N 12 Mean(SD)[mg/dL] 0.5 (0.94)
Mean Difference IV,Random,95% CI
Mean Difference IV,Random,95% CI -0.78 [ -1.35, -0.21 ]
Abel 1973
10
-2
-1
Favours ELAA
Favours glucose
Analysis 1.4. Comparison 1 Essential L-amino acids (ELAA) versus glucose, Outcome 4 Average slope of blood urea nitrogen.
Comparison: 1 Essential L-amino acids (ELAA) versus glucose Outcome: 4 Average slope of blood urea nitrogen
Study or subgroup
ELAA N Mean(SD)[mg/dL] -4.8 (11.2)
Abel 1973
11
-20
-10
10
20
Favours ELAA
Favours glucose
29
Analysis 1.5. Comparison 1 Essential L-amino acids (ELAA) versus glucose, Outcome 5 Serum creatinine.
Comparison: 1 Essential L-amino acids (ELAA) versus glucose Outcome: 5 Serum creatinine
Study or subgroup
ELAA N Mean(SD)[mg/dL] 6 (4)
Mean Difference IV,Random,95% CI -0.70 [ -4.05, 2.65 ]
Feinstein 1981
11
-10
-5
10
Favours ELAA
Favours glucose
Analysis 1.6. Comparison 1 Essential L-amino acids (ELAA) versus glucose, Outcome 6 Serum proteins.
Comparison: 1 Essential L-amino acids (ELAA) versus glucose Outcome: 6 Serum proteins
Study or subgroup
ELAA N Mean(SD)[g/dL] 5.7 (0.9)
Glucose N 5 Mean(SD)[g/dL] 6.1 (1)
Feinstein 1981
-2
-1
Favours ELAA
Favours glucose
30
Analysis 1.7. Comparison 1 Essential L-amino acids (ELAA) versus glucose, Outcome 7 Urea nitrogen appearance.
Comparison: 1 Essential L-amino acids (ELAA) versus glucose Outcome: 7 Urea nitrogen appearance
Study or subgroup
ELAA N Mean(SD)[g/d] 6.7 (7.2)
Glucose N 7 Mean(SD)[g/d] 10.4 (5.9)
Feinstein 1981
11
-10
-5
10
Favours ELAA
Favours glucose
Analysis 2.1. Comparison 2 High essential and nonessential amino acid (ENAA) nitrogen intake versus low essential amino acid (EAA) nitrogen intake, Outcome 1 Urea nitrogen appearance.
Comparison: 2 High essential and nonessential amino acid (ENAA) nitrogen intake versus low essential amino acid (EAA) nitrogen intake Outcome: 1 Urea nitrogen appearance
Study or subgroup
High ENAA N Mean(SD)[g/d] 14 (7.4)
Low EAA N 5 Mean(SD)[g/d] 7.5 (3)
Mean Difference IV,Random,95% CI 6.50 [ 0.02, 12.98 ]
Feinstein 1983
-20
-10
10
20
Favours high ENAA
Favours low EAA
31
Analysis 2.2. Comparison 2 High essential and nonessential amino acid (ENAA) nitrogen intake versus low essential amino acid (EAA) nitrogen intake, Outcome 2 Estimated protein nitrogen balance.
Comparison: 2 High essential and nonessential amino acid (ENAA) nitrogen intake versus low essential amino acid (EAA) nitrogen intake Outcome: 2 Estimated protein nitrogen balance
Study or subgroup
High ENAA N Mean(SD)[g/d] -3 (4)
Low EAA N 5 Mean(SD)[g/d] -5.2 (2.9)
Mean Difference IV,Random,95% CI 2.20 [ -1.89, 6.29 ]
Feinstein 1983
-10
-5
10
Favours high ENAA
Favours low EAA
Analysis 3.1. Comparison 3 Essential amino acids (EAA) versus general amino acids (GAA), Outcome 1 Death.
Comparison: 3 Essential amino acids (EAA) versus general amino acids (GAA) Outcome: 1 Death
Study or subgroup
EAA n/N
GAA n/N 6/24
Mirtallo 1982
8/21
0.2
0.5
Favours EAA
Favours GAA
32
Analysis 3.2. Comparison 3 Essential amino acids (EAA) versus general amino acids (GAA), Outcome 2 Estimated protein nitrogen balance.
Comparison: 3 Essential amino acids (EAA) versus general amino acids (GAA) Outcome: 2 Estimated protein nitrogen balance
Study or subgroup
EAA N Mean(SD)[g/d] 1.13 (1.06)
GAA N 17 Mean(SD)[g/d] 0.84 (1.02)
Mirtallo 1982
14
-2
-1
Favours EAA
Favours GAA
Analysis 3.3. Comparison 3 Essential amino acids (EAA) versus general amino acids (GAA), Outcome 3 Urea nitrogen appearance.
Comparison: 3 Essential amino acids (EAA) versus general amino acids (GAA) Outcome: 3 Urea nitrogen appearance
Study or subgroup
EAA N Mean(SD)[g/d] 4.18 (1.07)
GAA N 17 Mean(SD)[g/d] 3.2 (1)
Mirtallo 1982
14
-2
-1
Favours EAA
Favours GAA
33
Analysis 3.4. Comparison 3 Essential amino acids (EAA) versus general amino acids (GAA), Outcome 4 Net protein utilisation.
Comparison: 3 Essential amino acids (EAA) versus general amino acids (GAA) Outcome: 4 Net protein utilisation
Study or subgroup
EAA N Mean(SD)[%] 45.3 (22)
GAA N 17 Mean(SD)[%] 23.8 (37.2)
Mirtallo 1982
14
-50
-25
25
50
Favours EAA
Favours GAA
Analysis 4.1. Comparison 4 High-dose amino acids (AA) versus normal-dose AA, Outcome 1 Death.
Comparison: 4 High-dose amino acids (AA) versus normal-dose AA Outcome: 1 Death
Study or subgroup
High-dose AA n/N
Normal-dose AA n/N 2/6
Singer 2007
3/8
0.05
0.2
20
Favours high-dose AA
Favours normal-dose AA
34
Analysis 4.2. Comparison 4 High-dose amino acids (AA) versus normal-dose AA, Outcome 2 Haemodialysis requirement.
Comparison: 4 High-dose amino acids (AA) versus normal-dose AA Outcome: 2 Haemodialysis requirement
Study or subgroup
High-dose AA n/N
Normal-dose AA n/N 1/6
Singer 2007
2/8
0.05
0.2
20
Analysis 4.3. Comparison 4 High-dose amino acids (AA) versus normal-dose AA, Outcome 3 Cumulative nitrogen balance.
Comparison: 4 High-dose amino acids (AA) versus normal-dose AA Outcome: 3 Cumulative nitrogen balance
Study or subgroup
High-dose AA N Mean(SD)[g/d] 2.9 (8.3)
Normal-dose AA N 6 Mean(SD)[g/d] -10.5 (17)
Singer 2007
-50
-25
25
50
35
Analysis 4.4. Comparison 4 High-dose amino acids (AA) versus normal-dose AA, Outcome 4 Furosemide requirement.
Comparison: 4 High-dose amino acids (AA) versus normal-dose AA Outcome: 4 Furosemide requirement
Study or subgroup
High-dose AA N Mean(SD)[mg/d] 479 (293)
Normal-dose AA N 6 Mean(SD)[mg/d] 830 (288)
Singer 2007
-1000
-500
500
1000
Analysis 5.1. Comparison 5 Glucose+EAA+histidin versus glucose+GAA, Outcome 1 Nitrogen balance.

Comparison: 5 Glucose+EAA+histidin versus glucose+GAA Outcome: 1 Nitrogen balance
Study or subgroup Gluc+EAA+histidin N De Aguilar 1982 Martinez 1980 17 10 Mean(SD)[g/d] -0.5 (2.1) -0.57 (2.09)
Gluc+GAA N 23 13 Mean(SD)[g/d] 1.4 (1.4) 1.4 (1.38)
Weight
62.9 % 37.1 %
-1.90 [ -3.05, -0.75 ] -1.97 [ -3.47, -0.47 ]
Total (95% CI)
27
36
100.0 % -1.93 [ -2.84, -1.01 ]
Heterogeneity: Tau2 = 0.0; Chi2 = 0.01, df = 1 (P = 0.94); I2 =0.0% Test for overall effect: Z = 4.14 (P = 0.000035) Test for subgroup differences: Not applicable
-4
-2
Favs gluc+EAA+hist
Favs gluc+GAA
36
Analysis 5.2. Comparison 5 Glucose+EAA+histidin versus glucose+GAA, Outcome 2 Plasma urea.

Comparison: 5 Glucose+EAA+histidin versus glucose+GAA Outcome: 2 Plasma urea
Study or subgroup Gluc+EAA+histidin N De Aguilar 1982 Martinez 1980 17 10 Mean(SD)[g/L] 0.98 (0.55) 0.98 (0.55)
Gluc+GAA N 23 13 Mean(SD)[g/L] 0.83 (0.44) 0.83 (0.44)
Weight
63.3 % 36.7 %
0.15 [ -0.17, 0.47 ] 0.15 [ -0.27, 0.57 ]
Total (95% CI)
27
36
100.0 % 0.15 [ -0.10, 0.40 ]
-1
-0.5
0.5
Favs gluc+EAA+hist
Favs gluc+GAA
Analysis 5.3. Comparison 5 Glucose+EAA+histidin versus glucose+GAA, Outcome 3 U/P urea.

Comparison: 5 Glucose+EAA+histidin versus glucose+GAA Outcome: 3 U/P urea
Study or subgroup
Gluc+EAA+histidin N Mean(SD) 20.7 (9.3) 20.66 (9.25)
Gluc+GAA N 23 13 Mean(SD) 19.8 (13.2) 19.75 (13.23)
Weight
De Aguilar 1982 Martinez 1980
17 10
63.5 % 36.5 %
0.90 [ -6.07, 7.87 ] 0.91 [ -8.29, 10.11 ]
Total (95% CI)
27
36
100.0 % 0.90 [ -4.65, 6.46 ]
-20
-10
10
20
Favs gluc+EAA+hist
Favs gluc+GAA
37
Analysis 5.4. Comparison 5 Glucose+EAA+histidin versus glucose+GAA, Outcome 4 Serum creatinine.

Comparison: 5 Glucose+EAA+histidin versus glucose+GAA Outcome: 4 Serum creatinine
Study or subgroup Gluc+EAA+histidin N De Aguilar 1982 Feinstein 1981 Martinez 1980 17 11 10 Mean(SD)[mg/dL] 1.3 (0.6) 6 (4) 1.32 (0.58)
Gluc+GAA N 23 12 13 Mean(SD)[mg/dL] 1.2 (0.5) 8.1 (3.1) 1.24 (0.54)
Weight
61.6 % 1.0 % 37.4 %
0.10 [ -0.25, 0.45 ] -2.10 [ -5.04, 0.84 ] 0.08 [ -0.38, 0.54 ]
Total (95% CI)
38
48
100.0 % 0.07 [ -0.23, 0.37 ]
Heterogeneity: Tau2 = 0.01; Chi2 = 2.12, df = 2 (P = 0.35); I2 =6% Test for overall effect: Z = 0.47 (P = 0.64) Test for subgroup differences: Not applicable
-10
-5
10
Favs gluc+EAA+hist
Favs gluc+GAA
Analysis 5.5. Comparison 5 Glucose+EAA+histidin versus glucose+GAA, Outcome 5 Urea nitrogen appearance.
Comparison: 5 Glucose+EAA+histidin versus glucose+GAA Outcome: 5 Urea nitrogen appearance
Study or subgroup
Gluc+EAA+histidin N Mean(SD)[g/d] 6.7 (7.2)
Gluc+GAA N 12 Mean(SD)[g/d] 14 (8)
Feinstein 1981
11
-20
-10
10
20
Favs gluc+EAA+hist
Favs gluc+GAA
38
Analysis 5.6. Comparison 5 Glucose+EAA+histidin versus glucose+GAA, Outcome 6 Serum proteins.

Comparison: 5 Glucose+EAA+histidin versus glucose+GAA Outcome: 6 Serum proteins
Study or subgroup
Gluc+EAA+histidin N Mean(SD)[g/dL] 5.7 (0.9)
Gluc+GAA N 9 Mean(SD)[g/dL] 5 (0.6)
Feinstein 1981
-2
-1
Favs gluc+EAA+hist
Favs gluc+GAA
Analysis 6.1. Comparison 6 Glucose+EAA+histidin versus glucose+nitrogen+fat, Outcome 1 Nitrogen balance.

Comparison: 6 Glucose+EAA+histidin versus glucose+nitrogen+fat Outcome: 1 Nitrogen balance
Study or subgroup
Glucose+EAA+histidin N Mean(SD)[g/d] -0.5 (2.1) -0.57 (2.09)
Glucose+nitrogen+fat N 19 12 Mean(SD)[g/d] 1.6 (0.8) 1.62 (0.81)
Weight
17 10
62.6 % 37.4 %
-2.10 [ -3.16, -1.04 ] -2.19 [ -3.56, -0.82 ]
Total (95% CI)
27
31
100.0 % -2.13 [ -2.97, -1.29 ]
Heterogeneity: Tau2 = 0.0; Chi2 = 0.01, df = 1 (P = 0.92); I2 =0.0% Test for overall effect: Z = 4.98 (P < 0.00001) Test for subgroup differences: Not applicable
-4
-2
Favs gluc+EAA+hist
Favs gluc+nitrogen+fat
39
Analysis 6.2. Comparison 6 Glucose+EAA+histidin versus glucose+nitrogen+fat, Outcome 2 Plasma urea.

Comparison: 6 Glucose+EAA+histidin versus glucose+nitrogen+fat Outcome: 2 Plasma urea
Study or subgroup
Glucose+EAA+histidin N Mean(SD)[g/L] 0.98 (0.55) 0.98 (0.55)
Glucose+nitrogen+fat N 19 12 Mean(SD)[g/L] 0.58 (0.14) 0.58 (0.14)
Weight
17 10
62.9 % 37.1 %
0.40 [ 0.13, 0.67 ] 0.40 [ 0.05, 0.75 ]
Total (95% CI)
27
31
100.0 % 0.40 [ 0.19, 0.61 ]
-1
-0.5
0.5
Favs gluc+EAA+hist
Analysis 6.3. Comparison 6 Glucose+EAA+histidin versus glucose+nitrogen+fat, Outcome 3 U/P urea.

Comparison: 6 Glucose+EAA+histidin versus glucose+nitrogen+fat Outcome: 3 U/P urea
Study or subgroup
Glucose+EAA+histidin N Mean(SD) 20.7 (9.3) 20.66 (9.25)
Glucose+nitrogen+fat N 19 12 Mean(SD) 25.8 (10.2) 25.8 (10.2)
Weight
17 10
62.0 % 38.0 %
-5.10 [ -11.47, 1.27 ] -5.14 [ -13.27, 2.99 ]
Total (95% CI)
27
31
100.0 %
-5.12 [ -10.13, -0.10 ]
-20
-10
10
20
Favs gluc+EAA+histidin
40
Analysis 6.4. Comparison 6 Glucose+EAA+histidin versus glucose+nitrogen+fat, Outcome 4 Serum creatinine.

Comparison: 6 Glucose+EAA+histidin versus glucose+nitrogen+fat Outcome: 4 Serum creatinine
Study or subgroup
Glucose+EAA+histidin N Mean(SD)[mg/dL] 1.3 (0.6) 1.32 (0.58)
Glucose+nitrogen+fat N 19 12 Mean(SD)[mg/dL] 0.9 (0.3) 0.87 (0.3)
Weight
17 10
61.4 % 38.6 %
0.40 [ 0.08, 0.72 ] 0.45 [ 0.05, 0.85 ]
Total (95% CI)
27
31
100.0 % 0.42 [ 0.17, 0.67 ]
-1
-0.5
0.5
Favs gluc+EAA+hist
Analysis 7.1. Comparison 7 Glucose+GAA versus glucose+nitrogen+fat, Outcome 1 Nitrogen balance.

Comparison: 7 Glucose+GAA versus glucose+nitrogen+fat Outcome: 1 Nitrogen balance
Study or subgroup
Glucose+GAA N Mean(SD)[g/d] 1.4 (1.4) 1.4 (1.38)
Glucose+nitrogen+fat N 19 12 Mean(SD)[g/d] 1.6 (0.8) 1.62 (0.81)
Weight
23 13
62.9 % 37.1 %
-0.20 [ -0.88, 0.48 ] -0.22 [ -1.10, 0.66 ]
Total (95% CI)
36
31
100.0 % -0.21 [ -0.74, 0.33 ]
-4
-2
Favours glucose+GAA
Favours glucose+nitrogen+fat
41
Analysis 7.2. Comparison 7 Glucose+GAA versus glucose+nitrogen+fat, Outcome 2 Plasma urea.

Comparison: 7 Glucose+GAA versus glucose+nitrogen+fat Outcome: 2 Plasma urea
Study or subgroup
Glucose+GAA N Mean(SD)[g/L] 0.83 (0.44) 0.83 (0.44)
Glucose+nitrogen+fat N 19 12 Mean(SD)[g/L] 0.58 (1.4) 0.58 (1.4)
Weight
23 13
61.5 % 38.5 %
0.25 [ -0.40, 0.90 ] 0.25 [ -0.58, 1.08 ]
Total (95% CI)
36
31
100.0 % 0.25 [ -0.26, 0.76 ]
-2
-1
Favours glucose+GAA
Analysis 7.3. Comparison 7 Glucose+GAA versus glucose+nitrogen+fat, Outcome 3 U/P urea.

Comparison: 7 Glucose+GAA versus glucose+nitrogen+fat Outcome: 3 U/P urea
Study or subgroup
Glucose+GAA N Mean(SD) 19.8 (13.2) 19.75 (13.23)
Glucose+nitrogen+fat N 19 12 Mean(SD) 25.8 (10.2) 25.8 (10.2)
Weight
23 13
62.9 % 37.1 %
-6.00 [ -13.08, 1.08 ] -6.05 [ -15.27, 3.17 ]
Total (95% CI)
36
31
100.0 % -6.02 [ -11.63, -0.40 ]
-20
-10
10
20
Favours glucose+GAA
42
Analysis 7.4. Comparison 7 Glucose+GAA versus glucose+nitrogen+fat, Outcome 4 Serum creatinine.

Comparison: 7 Glucose+GAA versus glucose+nitrogen+fat Outcome: 4 Serum creatinine
Study or subgroup Glucose+GAA N De Aguilar 1982 Martinez 1980 23 13 Mean(SD)[mg/dL] 1.2 (0.5) 1.24 (0.54)
Glucose+nitrogen+fat N 19 12 Mean(SD)[mg/dL] 0.9 (0.3) 0.87 (0.3)
Weight
65.7 % 34.3 %
0.30 [ 0.06, 0.54 ] 0.37 [ 0.03, 0.71 ]
Total (95% CI)
36
31
100.0 % 0.32 [ 0.13, 0.52 ]
-1
-0.5
0.5
Favours glucose+GAA
APPENDICES Appendix 1. Electronic search strategies
Database CENTRAL
Search terms 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. MeSH descriptor Kidney Failure, Acute explode all trees (acute next kidney next failure):ti,ab,kw (acute next renal next failure):ti,ab,kw (ARF or AKF):ti,ab (#1 OR #2 OR #3 OR #4) MeSH descriptor Nutrition Therapy explode all trees MeSH descriptor Nutritional Requirements, this term only MeSH descriptor Energy Intake explode all trees MeSH descriptor Infusions, Parenteral explode all trees MeSH descriptor Intubation, Gastrointestinal, this term only MeSH descriptor Gastrostomy, this term only MeSH descriptor Dietary Proteins explode all trees MeSH descriptor Amino Acids explode all trees MeSH descriptor Glucose, this term only MeSH descriptor Food, Formulated, this term only
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16. (nutri* next support):ti,ab,kw 17. (nutri* next requirement*):ti,ab,kw 18. (protein* or glucose* or (amino next acid)):ti,ab 19. (naso-gastric* or nasogastric* or nose or tube* or ng or intravenous* or iv or parenteral* or enteral* or jejunal* or naso-jejunal* or nasojejunal*):ti,ab 20. (nitri* or feed* or food* or refeed* or refed* or re-fed* or diet* or hyperalimantation* or alimentation* or uid*) :ti,ab 21. (#19 AND #20) 22. ((energy next intake) or (energy next requirement)):ti,ab 23. (#6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #21 OR #22) 24. (#5 AND #23) 25. SR-RENAL 26. (#24 AND NOT #25) MEDLINE 1. exp Kidney Failure Acute/ 2. acute kidney failure.tw. 3. acute renal failure.tw. 4. (ARF or AKF).tw. 5. or/1-4 6. exp Nutrition Therapy/ 7. Nutritional Requirements/ 8. Energy Intake/ 9. Parenteral Infusions/ 10. Intubation Gastrointestinal/ 11. Gastrostomy/ 12. Dietary Proteins/ 13. Amino Acids/ 14. Glucose/ 15. Food Formulated/ 16. nutri$ support$.tw. 17. nutri$ requirement$.tw. 18. (protein$ or glucose or amino acid$).tw. 19. ((naso-gastric$ or nasogastric$ or nose or tube$ or ng or intravenous$ or iv$ or parenteral$ or enteral$ or jejunal$ or naso-jejunal$ or nasojejunal$) adj5 (nutri$ or feed$ or food$ or refeed$ or re-feed$ or refed$ or re-fed$ or diet$ or hyperalimentation$ or alimentation$ or uid$)).tw. 20. (energy intake or energy requirement$).tw. 21. or/6-20 22. and/5,21 1. 2. 3. 4. 5. 6. 7. 8. 9. Acute Kidney Failure/ Acute Kidney Tubule Necrosis/ acute kidney failure.tw. acute renal failure.tw. (arf or akf ).tw. or/1-5 Nutritional Support/ Diet Supplementation/ exp Parenteral Nutrition/
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EMBASE
(Continued)
10. Enteric Feeding/ 11. Amino Acid/ 12. exp Essential Amino Acid/ 13. exp Oxoacid/ 14. Gastrostomy/ 15. Protein/ 16. Glucose/ 17. nutri$ support$.tw. 18. nutri$ requirement$.tw. 19. (protein$ or glucose or amino acid$).tw. 20. ((naso-gastric$ or nasogastric$ or nose or tube$ or ng or intravenous$ or iv$ or parenteral$ or enteral$ or jejunal$ or naso-jejunal$ or nasojejunal$) adj5 (nutri$ or feed$ or food$ or refeed$ or re-feed$ or refed$ or re-fed$ or diet$ or hyperalimentation$ or alimentation$ or uid$)).tw. 21. or/7-20 22. and/6,21
Appendix 2. Risk of bias assessment tool
Potential source of bias
Assessment criteria
Random sequence generation Low risk of bias: Random number table; computer random numSelection bias (biased allocation to interventions) due to inade- ber generator; coin tossing; shufing cards or envelopes; throwing quate generation of a randomised sequence dice; drawing of lots; minimization (minimization may be implemented without a random element, and this is considered to be equivalent to being random) High risk of bias: Sequence generated by odd or even date of birth; date (or day) of admission; sequence generated by hospital or clinic record number; allocation by judgement of the clinician; by preference of the participant; based on the results of a laboratory test or a series of tests; by availability of the intervention Unclear: Insufcient information about the sequence generation process to permit judgement Allocation concealment Low risk of bias: Randomisation method described that would not Selection bias (biased allocation to interventions) due to inade- allow investigator/participant to know or inuence intervention quate concealment of allocations prior to assignment group before eligible participant entered in the study (e.g. central allocation, including telephone, web-based, and pharmacy-controlled, randomisation; sequentially numbered drug containers of identical appearance; sequentially numbered, opaque, sealed envelopes) High risk of bias: Using an open random allocation schedule (e.g. a list of random numbers); assignment envelopes were used without appropriate safeguards (e.g. if envelopes were unsealed or nonNutritional support for acute kidney injury (Review) Copyright 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 45
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opaque or not sequentially numbered); alternation or rotation; date of birth; case record number; any other explicitly unconcealed procedure Unclear: Randomisation stated but no information on method used is available Blinding of participants and personnel Low risk of bias: No blinding or incomplete blinding, but the rePerformance bias due to knowledge of the allocated interventions view authors judge that the outcome is not likely to be inuenced by participants and personnel during the study by lack of blinding; blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken High risk of bias: No blinding or incomplete blinding, and the outcome is likely to be inuenced by lack of blinding; blinding of key study participants and personnel attempted, but likely that the blinding could have been broken, and the outcome is likely to be inuenced by lack of blinding Unclear: Insufcient information to permit judgement Blinding of outcome assessment Low risk of bias: No blinding of outcome assessment, but the review Detection bias due to knowledge of the allocated interventions by authors judge that the outcome measurement is not likely to be outcome assessors inuenced by lack of blinding; blinding of outcome assessment ensured, and unlikely that the blinding could have been broken High risk of bias: No blinding of outcome assessment, and the outcome measurement is likely to be inuenced by lack of blinding; blinding of outcome assessment, but likely that the blinding could have been broken, and the outcome measurement is likely to be inuenced by lack of blinding Unclear: Insufcient information to permit judgement Incomplete outcome data Low risk of bias: No missing outcome data; reasons for missing Attrition bias due to amount, nature or handling of incomplete outcome data unlikely to be related to true outcome (for survival outcome data data, censoring unlikely to be introducing bias); missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk not enough to have a clinically relevant impact on the intervention effect estimate; for continuous outcome data, plausible effect size (difference in means or standardized difference in means) among missing outcomes not enough to have a clinically relevant impact on observed effect size; missing data have been imputed using appropriate methods
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High risk of bias: Reason for missing outcome data likely to be related to true outcome, with either imbalance in numbers or reasons for missing data across intervention groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk enough to induce clinically relevant bias in intervention effect estimate; for continuous outcome data, plausible effect size (difference in means or standardized difference in means) among missing outcomes enough to induce clinically relevant bias in observed effect size; as-treated analysis done with substantial departure of the intervention received from that assigned at randomisation; potentially inappropriate application of simple imputation Unclear: Insufcient information to permit judgement Selective reporting Reporting bias due to selective outcome reporting Low risk of bias: The study protocol is available and all of the studys pre-specied (primary and secondary) outcomes that are of interest in the review have been reported in the pre-specied way; the study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre-specied (convincing text of this nature may be uncommon) High risk of bias: Not all of the studys pre-specied primary outcomes have been reported; one or more primary outcomes is reported using measurements, analysis methods or subsets of the data (e.g. subscales) that were not pre-specied; one or more reported primary outcomes were not pre-specied (unless clear justication for their reporting is provided, such as an unexpected adverse effect); one or more outcomes of interest in the review are reported incompletely so that they cannot be entered in a metaanalysis; the study report fails to include results for a key outcome that would be expected to have been reported for such a study Unclear: Insufcient information to permit judgement Other bias Bias due to problems not covered elsewhere in the table Low risk of bias: The study appears to be free of other sources of bias. High risk of bias: Had a potential source of bias related to the specic study design used; stopped early due to some data-dependent process (including a formal-stopping rule); had extreme baseline imbalance; has been claimed to have been fraudulent; had some other problem Unclear: Insufcient information to assess whether an important risk of bias exists; insufcient rationale or evidence that an identied problem will introduce bias
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WHATS NEW
Last assessed as up-to-date: 4 July 2012.
Date 19 July 2012
Event Review declared as stable
Description As of July 2012 this Cochrane Review is no longer being updated. There have been no new studies published on this topic in the past ve years and there are currently no registered ongoing studies
HISTORY
Protocol rst published: Issue 3, 2005 Review rst published: Issue 1, 2010
Date 4 July 2012
Event New citation required but conclusions have not changed
Description New search performed; methodology updated; risk of bias tables completed We searched for new studies and 32 potential reports were identied. None of these reports fullled our inclusion criteria and were excluded
4 July 2012
New search has been performed
CONTRIBUTIONS OF AUTHORS
All four authors contributed to develop the review. 1. Draft the protocol: Li Y, Wu T 2. Study selection: Tang X, Li Y 3. Extract data from studies: Zhang J, Li Y 4. Enter data into RevMan: Li Y 5. Carry out the analysis: Li Y, Wu T 6. Interpret the analysis: Wu T 7. Draft the nal review: Li Y, Tang X 8. Disagreement resolution: Wu T 9. Update the review: Li Y
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DECLARATIONS OF INTEREST
None known.
DIFFERENCES BETWEEN PROTOCOL AND REVIEW

Risk of bias assessment toll has replaced quality assessment checklist (Wu 2005).
INDEX TERMS Medical Subject Headings (MeSH)

Acute Kidney Injury [ therapy]; Amino Acids, Essential [administration & dosage]; Dietary Proteins [administration & dosage]; Enteral Nutrition [ methods]; Glomerular Filtration Rate; Glucose Solution, Hypertonic [administration & dosage]; Parenteral Nutrition, Total [ methods]; Randomized Controlled Trials as Topic
MeSH check words

Humans
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Nutritional Support For Acute Kidney Injury (Review) : Li Y, Tang X, Zhang J, Wu T

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Nutritional support for acute kidney injury (Review)

Nutritional support for acute kidney injury

Description of the condition

Description of the intervention

METHODS How the intervention might work

Criteria for considering studies for this review

Why it is important to do this review

Additional outcome measures

Search methods for identication of studies

Types of outcome measures

Kidney function measures

Nutritional status measures

Adverse effect outcome measures

Glucose level Triglycerides level Insulin use Volume Catheter infection

Data collection and analysis

Figure 1. Study ow diagram of included studies

Risk of bias in included studies

None of the studies provided any information about allocation concealment.

Recovery from AKI

Average slope of BUN (mg/dL)

Serum proteins (g/dL)

Urea nitrogen appearance (g/d)

Urea nitrogen appearance (g/d)

Nitrogen balance (g/d)

Estimated protein nitrogen balance (g/d)

Furosemide requirement (mg/d)

Nitrogen balance (g/d)

Plasma urea (g/L)

U/P urea Plasma urea (g/L)

Urea nitrogen appearance (g/d)

Nitrogen balance (g/d)

Plasma urea (g/L) Serum proteins (g/dL)

Nitrogen balance (g/dL)

Overall completeness and applicability of evidence

Summary of main results

Quality of the evidence

Potential biases in the review process

AUTHORS CONCLUSIONS Implications for practice

Implications for research

Agreements and disagreements with other studies or reviews

References to studies included in this review

References to studies excluded from this review

failure. Clinical Nutrition 1997;16(5):23946. [EMBASE: 1998017394]

References to other published versions of this review

Characteristics of included studies [ordered by study ID]

No patients missing from either group

Selective reporting (reporting bias) Other bias De Aguilar 1982 Methods

Unclear risk Low risk

No measurements listed in methods No conict of interest

Notes Risk of bias Bias

The statistical analysis used was a t-test of matched data.

Support for judgement Not stated

Not stated Not stated

No patients missing from either group

Selective reporting (reporting bias)

Measurements listed in methods were all reported No conict of interest

Other bias Feinstein 1981 Methods

No patients missing from either group

Outcome measurements listed in methods were all reported No conict of interest

Other bias Feinstein 1983 Methods

Not stated Not stated

No patients missing from either group